Management of Tricuspid Valve Regurgitation During Surgical Ventricular Restoration for Ischemic Cardiomyopathy

Introduction We studied the effect of tricuspid valve (TV) surgery combined with surgical ventricular restoration (SVR) on operative outcomes, rehospitalization, recurrent tricuspid regurgitation, and survival of patients with ischemic cardiomyopathy. Additionally, surgery was compared to conservative management in patients with mild or moderate tricuspid regurgitation. To the best of our knowledge, the advantage of combining TV surgery with SVR in patients with ischemic cardiomyopathy had not been investigated before. Methods This retrospective cohort study included 137 SVR patients who were recruited from 2009 to 2020. Patients were divided into two groups - those with no concomitant TV surgery (n=74) and those with concomitant TV repair or replacement (n=63). Results Extracorporeal membrane oxygenation use was higher in SVR patients without TV surgery (P=0.015). Re-exploration and blood transfusion were significantly higher in those with TV surgery (P=0.048 and P=0.037, respectively). Hospital mortality occurred in eight (10.81%) patients with no TV surgery vs. five (7.94%) in the TV surgery group (P=0.771). Neither rehospitalization (log-rank P=0.749) nor survival (log-rank P=0.515) differed in patients with mild and moderate tricuspid regurgitation in both groups. Freedom from recurrent tricuspid regurgitation was non-significantly higher in mild and moderate tricuspid regurgitation patients with no TV surgery (P=0.059). Conservative management predicted the recurrence of tricuspid regurgitation. Conclusion TV surgery concomitant with SVR could reduce the recurrence of tricuspid regurgitation; however, its effect on the clinical outcomes of rehospitalization and survival was not evident. The same effects were observed in patients with mild and moderate tricuspid regurgitation.


INTRODUCTION
Surgical ventricular restoration (SVR) is the intended procedure to correct the abnormal geometrical alterations following myocardial ischemia [1] . Ischemic cardiomyopathy may result in several changes, including abnormal spherical rather than elliptical shape, increased ventricular size, and reduced ventricular function [2] . Restoring the normal anatomical shape, reducing the size of the enlarged ventricle, revascularization, and treatment of valvulopathies would be targeted following ischemia. Some studies proposed the importance of achieving normal left ventricular (LV) volume by SVR rather than focusing on improving ejection fraction (EF) alone by revascularization procedures [3] . The importance of SVR procedures in patients with ischemic cardiomyopathy or heart failure has become a great concern, especially in nations where heart transplantation is still limited or less frequently performed [1,4] . SVR was usually performed following anterior myocardial infarction with consequent LV end-systolic volume index > 60 ml/m 2 [5] . Several techniques have evolved, and further studies are recommended to understand better the effectiveness and long-term outcomes of the different SVR procedures. Prucz et al. conducted a study to compare the effects of combining SVR with coronary artery bypass grafting (CABG) vs. CABG alone in patients with ischemic cardiomyopathy and enlarged ventricular size. The study showed less rehospitalization in patients with SVR and CABG and better improvements in New York Heart Association (NYHA) class [6] . Another study showed a decrease in mitral regurgitation (MR) grade by combining SVR and CABG [7] . Few studies discussed the impact of combining mitral surgery with SVR. Castelvecchio et al. found that early and mid-term outcomes of combining SVR and mitral repair can be predicted according to angina symptoms before surgery [8] . However, combining SVR and tricuspid valve (TV) surgery was not explored earlier. SVR patients are high-risk patients [9] , and it is unknown whether adding additional TV intervention with prolonged operative and cardiopulmonary bypass times could lead to improved immediate and long-term outcomes. In this study, we aimed to investigate the effect of combining TV surgery with SVR on operative outcomes and long-term cardiac rehospitalization, recurrent tricuspid regurgitation (TR), and survival of patients with ischemic cardiomyopathy. Additionally, we compared TV surgery vs. conservative management in patients with mild or moderate TR.

Study Design
We conducted a retrospective cohort study including 137 patients who underwent SVR for ischemic cardiomyopathy from November 2009 to October 2020. Patients were divided according to the TV

Study Data and Outcomes
Preoperative data were collected according to European System for Cardiac Operative Risk Evaluation (EuroSCORE) II definitions [10] . Concomitant CABG and mitral valve surgery were reported. Study outcomes were hospital complications and long-term freedom from cardiac rehospitalization, recurrent TR, and survival. Surgical techniques used for SVR in our center were reported before by Calafiore et al. [11] . TV repair was performed using the DeVega technique (n=9), MC3™ rigid ring (Edwards Lifesciences, Irvine, California, United States of America) (n=1), and SMN50 flexible band (Sovering MiniBand, SMN50, Sorin, Saluggia, Italy) (n=51). For patients who had TV replacement, tissue valves were used (n=2). The patients were followed clinically after discharge for one and six months, then at yearly intervals, and the closing follow-up date was May 2020.

Echocardiography
All patients had transthoracic echocardiograms before surgery and at discharge. A total of 495 echocardiography examinations were available for all patients during a 10-year follow-up. Changes in EF, pulmonary artery systolic pressure (PASP), and right ventricular (RV) dilatation were reported and compared between groups.

Statistical Analysis
Analysis was performed using Stata 16 Multivariable Cox regression with backward elimination was used to identify factors affecting survival. The entry P-value was 0.1, and the stay P-value was 0.05. Fine and Gray method was used to perform competing risk regression [12] . Death was considered a competing risk for recurrent TR and cardiac rehospitalization. Choosing the final model of multivariable competing regression was performed in the same method as Cox regression.
Random effect regression was used to compare the change in EF and PASP over time between both groups. Random effect ordinal logistic regression was used to compare the change in the degree of RV dilatation.

Operative Data
There were no differences in operative status, concomitant CABG, and the number of anastomoses between groups. Concomitant mitral valve replacement was more common in patients with TV surgery (P<0.001). Septal reshaping was the most common technique used in the TV surgery group (P=0.001), while septal reshaping and septoapical Dor procedure were performed more commonly in the no TV surgery group. Cardiopulmonary bypass and ischemic times were significantly longer in TV surgery patients (P=0.043 and P=0.026, respectively) ( Table 3).

Postoperative Outcomes
Extracorporeal membrane oxygenation (ECMO) use was higher in SVR patients without concomitant TV surgery (P=0.015). TV surgery patients had significantly more re-exploration for tamponade and received more red blood cell (RBC) units (P=0.048 and P=0.037, respectively). There was no difference in other postoperative complications between groups. Hospital mortality occurred in eight (10.81%) patients who did not undergo TV surgery vs. five (7.94%) patients with TV surgery (P=0.771) ( Table 4).

Long-Term Outcomes
Median follow-up time was 57 (21.57-99) months. Three patients required reintervention, one had TV repair (TV surgery group), and two had a mitral valve replacement (one from each group). Four    Figure 1A). There was no difference in rehospitalization in patients with mild and moderate TR from both groups (log-rank P=0.749) ( Figure 1B). High PASP, low EF, and patients with no concomitant CABG were associated with increased rehospitalization (Table 5). Freedom from recurrent grade II or higher TR did not differ between groups (log-rank P=0.499) (Figure 2A). Freedom from recurrent TR in patients with preoperative mild or moderate TR was non-significantly higher in patients with no TV surgery (log-rank P=0.059) ( Figure 2B). Factors associated with recurrent TR were low EF, high PASP, and TV surgery; CABG was protective (Table 5). Thirty-seven mortalities occurred during follow-up time -18 in patients with no TV surgery and 19 in the TV surgery group. Survival at one, three, five, and eight years was 84.86%, 77.22%, 77.22%, and 74.95%, respectively, in no TV surgery group and 83.51%, 72.80%, 67.58%, and 64.64%, respectively, in the TV surgery group (logrank P=0.394) ( Figure 3A). There was no difference in mortality in patients with mild and moderate TR between groups (log-rank P=0.515). Factors affecting long-term survival were age, recent MI, high bilirubin level, emergency operation, and prolonged cardiopulmonary bypass time (Table 5).     ventricular volume measurements to predict post-MI mortality rather than solely depending on the EF. The study showed five times higher post-MI mortality when the LV end-systolic volume index was > 60 ml/m 2 [13] . In SVR, reducing the LV size and maintaining a normal range of indexed LV end-systolic volume were targeted. It has shown better results when combined with coronary revascularization procedures [13] . Logically, increased volume will increase pressure, dilatation, and valvular regurgitation. The end-diastolic diameter was higher in our study in the TV surgery group, and we expect higher intraventricular pressure and significant ventricular dilatation. In our study, a significant dilatation was associated with higher grades of TR. The resultant dilatation can also be illustrated by the increase in annular diameter and MR, which explains our results of higher MR grades and concomitant mitral valve surgery that were noticed in SVR with TV intervention. Several factors can indicate the need for TV surgical intervention, including the severity of the TR and PASP [8] . Those two factors were also higher in the TV surgery group. Different surgical interventions were attempted to improve heart function, including revascularization with CABG, correcting valvulopathies, partial LV No financial support. No conflict of interest. resection, implanting assisting devices, or heart transplantation as an end-stage solution [14] . Prucz et al. [6] conducted a study that showed combining revascularization and SVR had reduced longterm rehospitalization and improved long-term functional status.

Echocardiographic Follow-Up
Although it was proved that surgical correction of mitral valve regurgitation would improve the abnormal ventricular geometry in ischemic cardiomyopathy patients with reduced EF, a study showed that SVR alone could restore normal ventricular architecture without mitral valve repair [15] . Partial LV ventriculectomy was associated with unsatisfactory results, including a high hospital mortality rate and unrecovered LV function [16] . Several techniques were identified for SVR procedures. Septal reshaping was proved to reduce LV volume and MR and to significantly improve functional NYHA class in about 72% of the studied patients [17] . Septal reshaping was the most commonly used technique in the TV surgery group. However, septoapical Dor technique was used at the same rate as septal reshaping in the group of patients without TV surgery. Repairing or replacing the TV would consume more operative time, which can explain the significantly longer ischemic and cardiopulmonary bypass times in the TV surgery group. We expect to achieve better hemodynamic status postoperatively after correcting concomitant valve lesions. Thus, SVR in the TV surgery group required a significantly lower ECMO use. Nevertheless, combining several surgical interventions may increase the operation complexity, complications, and the need for re-exploration. We have a significantly higher rate of postoperative re-exploration for tamponade and a higher number of transfused RBC units in SVR with TV surgery. Concerning our long-term outcomes, the two groups were almost similar in terms of the need for further intervention and the incidence of stroke. Meanwhile, the rehospitalization rate was not significantly different between patients with mild or moderate TR in both groups. TR recurrence was insignificantly higher in patients with preoperative mild and moderate TR in the SVR without TV surgery group. A study that Lin et al. conducted found that recurrence of TR was associated with preoperative atrial fibrillation, severe TR, DeVega annuloplasty, postoperative permanent pacemaker insertion, and low preoperative EF, similarly to our findings [18] . Low EF and high PASP were risk factors for rehospitalization in our study. In addition, the lack of revascularization with CABG contributed to the overall incidence of rehospitalization. A research by Prucs et al. [6] showed that combining CABG with SVR has a lower rehospitalization rate, estimated to be 24%, compared to the 55% rate in the group without CABG. Our study did not show any significant difference between the two groups in terms of mortality. This may indicate that combining TR surgery with SVR is a relatively safe practice. In our research, both repair and replacement were considered in one group due to the limited number of cases. We suppose that having more cases and separating the two methods would give a better understanding of a better management strategy for concomitant TV disease during SVR.

Limitations
The study is limited by the retrospective design with its inherent referral and selection biases. Moreover, this is a single-center study, and generalization of the results might be an issue. There are several risk factors that have affected the outcomes or patients' selection and were not measured routinely.

CONCLUSION
TV surgery concomitant with SVR is safe procedure, with similar operative mortality compared to the conservative approach. Concomitant TV surgery could reduce the recurrence of TR; however, its effect on the clinical outcomes of rehospitalization and survival was not evident. The same effect was observed in patients with mild and moderate TV regurgitation.